The colour of human skin depends on many factors and especially on race and sex, but also on environmental factors (season, exposure to sunlight, etc.); it is mainly dependent on the nature and concentration of melanin produced by the melanocytes. Melanocytes are specialized cells that synthesize melanin, using particular organelles, the melanosomes. Certain individuals naturally or accidentally have more or less localized pigmentation defects, requiring palliative local treatments, or demand more general treatments, for stimulating natural pigmentation.
Pigmentation is a natural effective protection against the harmful effects of ultraviolet radiation and against light-induced ageing of the skin in general. Skin pigmentation is also a protection against the onset of skin cancers; for the same magnitude of exposure to sunlight, dark-skinned individuals and ethnic groups develop far fewer skin cancers than individuals with pale skin.
Similarly, the colour of body hair and head hair is due to melanin. At different periods in their life, especially during ageing, certain people develop gradual depigmentation of their head hair, with a reduction in or even the stoppage of the melanogenesis process in the melanocytes associated with the hair bulbs. It would be very advantageous to be able to propose preventive or curative treatments capable of maintaining the process of pigmentation of the hair or of stimulating melanogenesis and pigmentation of hair with a tendency towards greying.
Exposure to sunlight and UV radiation have harmful effects on the hair, not only on the hair stem (oxidation and bleaching), but also, and more destructively, on the hair bulb, which may lead to loss of the hair. The recovery or stimulation of hair follicle pigmentation is capable of limiting the loss of the hair or of stimulating its regrowth. The use of harmless pro-pigmenting substances, by topical or systemic application in compositions, and which show good efficacy, is most particularly sought in order to treat natural regional hypopigmentations (of genetic origin, leukodermias such as vitiligo, and ageing) or accidental regional hypopigmentations (post-lesional scars or fungal mycoses), and also the stress-related loss of hair pigmentation or loss in the course of ageing.
The use of harmless substances, by topical or systemic application in compositions, and which protect the hair, limit its loss and/or stimulate its regrowth, under normal conditions, stress conditions, conditions of exposure to sunlight and/or in the course of ageing, is also of major interest.
The mechanism of formation of skin pigmentation is complex and schematically involves the following main steps:
tyrosine→dopa→dopaquinone→dopachrome→melanin.
Melanin is stored in organites or melanosomes, and then transferred to the neighbouring keratinocytes.
Each of these steps is essential to pigmentation. Tyrosinase (monophenol dihydroxyl phenylalanine: oxygen oxidoreductase EC 1.14.18.1) is the first enzyme involved in this sequence of reactions. It especially catalyses the reaction for transformation of tyrosine to dopa (dihydroxyphenylalanine) by virtue of its hydroxylase activity, and the reaction for transformation of dopa to dopaquinone via its oxidase activity. This tyrosinase acts only when it is in the mature state, under the action of certain biological factors; signalling via specific receptors such as the melanocortin receptors (MCR) is involved for induction of the melanin synthesis process by the melanocytes, especially the receptor MC1R.
In the epidermis, the melanocyte is involved in the epidermal melanic unit, which comprises a melanocyte surrounded by about 36 neighbouring keratinocytes. All individuals, without distinction as to phototype, have approximately the same number of melanocytes for a given area of skin. The ethnic differences, in terms of pigmentation, are not due to the number of melanocytes, but to the properties of their melanosomes. The melanosomes are aggregated as complexes and are of small size. They are highly specialized organelles whose sole function is to produce melanin. Gradually, as melanin is synthesized in the melanosomes, they move from the perinuclear region to the extremity of the melanocytes' dendrites. Via phagocytosis, the extremity of the dendrites is captured by the keratinocytes, and the melanosomes are redistributed in the keratinocytes. The dendritic extensions of the melanocytes, and the phagocytic activity of the keratinocytes, thus play an essential role in the transfer of melanin. Melanosome transfer is a phagocytic phenomenon considered as standard, which involves receptors known as the “protease-activated receptor 2” (PAR-2).
Although the level of melanin varies from one population to another, the amount of tyrosinase does not vary significantly and the level of tyrosinase messenger RNA is identical in white or black skin. The variations in melanogenesis are thus due to variations either in tyrosinase activity or in the capacity of the keratinocytes to phagocytose the melanosomes. This indicates that the keratinocyte is a major player in pigmentation; 1) it is quantitatively the major representative of the melanic unit, and is also the agent that influences, via information molecules (cytokines and hormones), a large proportion of the melanogenic activity; 2) it is its capacity for phagocytosis, combined with an adequate presentation of the melanosomes, in a dense dendritic network, which allows optimum distribution of melanin in the epidermis and pigmentation.
A substance is recognized as being pro-pigmenting if it acts directly or indirectly on activation of the melanin synthesis process, and/or if it stimulates the melanosome phagocytosis capacity by the keratinocytes.
Substances such as α-melanotropin (α-melanocyte-stimulating hormone, α-MSH) and corticotropin (adrenocorticotropic hormone, ACTH) stimulate melanin proliferation and synthesis by the melanocytes, via binding to specific receptors, especially the receptor MC1-R.
Few natural inducers are currently available and used for natural melanic pigmentation of the skin or the hair.